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卵巢癌中新辅助化疗诱导的免疫重塑:对 TIL 动态与联合免疫治疗的启示

英文原题:Neoadjuvant chemotherapy-induced immune remodeling in ovarian cancer: implications for TIL dynamics and combination immunotherapy.

查看英文原题

Neoadjuvant chemotherapy-induced immune remodeling in ovarian cancer: implications for TIL dynamics and combination immunotherapy.

PubMed 2026/02/19(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

卵巢癌(OC),尤其是高级别浆液性卵巢癌(HGSOC),是最致命的妇科恶性肿瘤之一,其治疗挑战主要源于独特的免疫抑制性肿瘤免疫微环境(TIME)。新辅助化疗(NACT)已成为晚期卵巢癌的重要治疗策略;然而,其对肿瘤微环境——尤其是对TIL(肿瘤浸润淋巴细胞)(TILs)——的影响尚未完全阐明。作为抗肿瘤免疫应答的核心介质,TILs的密度、组成及动态变化与化疗反应和患者预后密切相关。

值得注意的是,空间组学研究进一步揭示,NACT后,一部分CD8+ T细胞可被限制在由髓系细胞组织形成的“髓系网”微结构域内,其中NECTIN2-TIGIT等相互作用施加空间限制并诱导T细胞功能性耗竭,从而损害其有效的肿瘤杀伤能力。本综述旨在系统总结卵巢癌中淋系和髓系来源TILs的基线特征及异质性,阐明NACT诱导免疫重塑的机制及其与临床结局的复杂关系,并进一步探讨基于TIL动态变化的联合治疗策略和生物标志物开发,以增强精准免疫治疗的临床应用。

展开英文摘要原文

Ovarian cancer (OC), particularly high-grade serous ovarian cancer (HGSOC), is among the most lethal gynecologic malignancies, with its therapeutic challenges primarily stemming from a distinctly immunosuppressive tumor immune microenvironment (TIME).

Neoadjuvant chemotherapy (NACT) has emerged as a crucial treatment strategy for advanced ovarian cancer; nevertheless, its impact on the tumor microenvironment-especially on tumor-infiltrating lymphocytes (TILs)-is not yet fully understood. As central mediators of antitumor immune responses, the density, composition, and dynamic changes of TILs are strongly associated with chemotherapy response and patient prognosis.

Notably, spatial omics studies further revealed that, after NACT, a subset of CD8+ T cells can be confined within "myelonets" microdomains organized by myeloid cells, where interactions such as NECTIN2-TIGIT impose spatial restriction and induce functional exhaustion of T cells, thereby compromising their effective tumor killing.

This review aims to systematically summarize the baseline characteristics and heterogeneity of lymphoid- and myeloid-derived TILs in ovarian cancer, elucidate the mechanisms underlying immune remodeling induced by NACT and their complex relationships with clinical outcomes, and further discuss combination therapeutic strategies and biomarker development based on dynamic TIL changes to enhance the clinical application of precision immunotherapy.

论文信息

作者
Zhu W、Li J、Sun Y、Lin Q、Sun Y、Xue M、Zheng C、Zhi X
单位
Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai, China.China
文献类型
综述
期刊
Frontiers in immunology2026
原文标识
PubMed 41798957 · DOI 10.3389/fimmu.2026.1757366